Otitis media with effusion : key factors
Otitis media with effusion (OME) is a disease characterised by inflammation of the middle ear and changes in middle ear mucosa from a columnar to a more secretory type epithelium, with a proliferation of goblet cells and mucus glands. There is excessive production of mucus, resulting in the accumulation of a viscous effusion in the middle ear cleft. Various factors have been implicated in the aetiology of the disease including bacteria, Eustachian tube dysfunction, allergy and craniofacial abnormalities. It has been suggested that laryngopharyngeal reflux could be an inflammatory co-factor and possible cause of many upper respiratory disorders including OME. The aims of this thesis were to examine effusions for the presence of gastric juice and were also concerned with the biochemical and rheological characterisation of effusions. Acidic proteinase (pepsin) activity measured at pH2.2 using the N-terminal assay was detected in 29% of effusions and 91% of these samples contained pepsin/pepsinogen protein at elevated levels compared to serum (using an ELISA). As other serum protein levels in effusions were of the same order as serum reference levels, the source of the activity was unlikely to be from a transudate of plasma and rather due to the reflux of gastric contents into the middle ear. The data suggests that reflux may be a primary factor in the initiation of OME in children. Middle ear effusions are mucin-rich secretions that demonstrate a lack of degradation on storage. They contained at least two distinct mucin populations, MUC5B is the major mucin and MUC5AC is present at much lower levels. MUC5B had a significant correlation with effusion specific viscosity suggesting that it is responsible for the rheological properties of the effusion. Interleukin-8 (IL-8) levels in effusions had significant correlation with MUC5AC and it may be that MUC5AC is produced in response to IL-8 in the middle ear during the inflammatory process of glue ear. Neither IL-6 nor IL-8 levels correlated with MUC5B content. It is likely that a different stimulus or other cytokine is responsible for the regulation of MUCSB. There was a significant correlation between IL-6 and IL-8 levels in effusions demonstrating that one cytokine could stimulate the secretion of the other. Further studies developing from the work presented in this thesis would involve analysis of effusions for other components of gastric juice, such as gastric lipase and intrinsic factor, to confirm the role of reflux in OME. A study following children from the diagnosis stage through the disease course and grommet insertion for glue ear with awareness of signs and symptoms of reflux would assess the proportion of children with glue ear associated with reflux. An animal model for reflux could be set up, instilling gastric juice components into the middle ear via the nasopharynx/ET to see if an effusion develops. Effusions could be analysed for other cytokines (such as IL-10 or TNF-a) to see if levels correlate with MUC5B content.